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Background Neuropsychiatric symptoms (NPS) are common in individuals with Alzheimer’s disease (AD) dementia, but substantial heterogeneity exists in the manifestation of NPS. Sex differences may explain this clinical variability. We aimed to investigate the sex differences in the prevalence and severity of NPS in AD dementia. Methods Literature searches were conducted in Embase, MEDLINE/PubMed, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar from inception to February 2021. Study selection, data extraction, and quality assessment were conducted in duplicate. Effect sizes were calculated as odds ratios (OR) for NPS prevalence and Hedges’ g for NPS severity. Data were pooled using random-effects models. Sources of heterogeneity were examined using meta-regression analyses. Results Sixty-two studies were eligible representing 21,554 patients (61.2% females). The majority of the included studies had an overall rating of fair quality (71.0%), with ten studies of good quality (16.1%) and eight studies of poor quality (12.9%). There was no sex difference in the presence of any NPS ( k = 4, OR = 1.35 [95% confidence interval 0.78, 2.35]) and overall NPS severity ( k = 13, g = 0.04 [− 0.04, 0.12]). Regarding specific symptoms, female sex was associated with more prevalent depressive symptoms ( k = 20, OR = 1.60 [1.28, 1.98]), psychotic symptoms (general psychosis k = 4, OR = 1.62 [1.12, 2.33]; delusions k = 12, OR = 1.56 [1.28, 1.89]), and aberrant motor behavior ( k = 6, OR = 1.47 [1.09, 1.98]). In addition, female sex was related to more severe depressive symptoms ( k = 16, g = 0.24 [0.14, 0.34]), delusions ( k = 10, g = 0.19 [0.04, 0.34]), and aberrant motor behavior ( k = 9, g = 0.17 [0.08, 0.26]), while apathy was more severe among males compared to females ( k = 11, g = − 0.10 [− 0.18, − 0.01]). There was no association between sex and the prevalence and severity of agitation, anxiety, disinhibition, eating behavior, euphoria, hallucinations, irritability, and sleep disturbances. Meta-regression analyses revealed no consistent association between the effect sizes across studies and method of NPS assessment and demographic and clinical characteristics. Discussion Female sex was associated with a higher prevalence and greater severity of several specific NPS, while male sex was associated with more severe apathy. While more research is needed into factors underlying these sex differences, our findings may guide tailored treatment approaches of NPS in AD dementia.

The terminology used to describe components of social cognition lacks clarity and specificity. Recent studies have tried to reach consensus on definitions of social cognition based on expert opinion. These efforts resulted in semantically well-defined terms and distinct concepts, but it remains unclear whether these terms also align with empirical data and existing theoretical models of social cognition. In this commentary, we examine whether the proposed definitions for social cognition are supported by clinical observations and the extant knowledge base on the underlying neural substrates of these skills. In addition, we consider how the proposed definitions align with existing theoretical models of social cognition. We argue that consensus should not be based solely on expert opinion. Therefore, we propose an updated biopsychosocial model of social cognition that integrates proposed expert definitions with a theoretical model of social cognition based on empirical data: the Hierarchical Interdependent Taxonomy of Social cognition (HITS) model. The HITS model guides future research, helps to address the poor construct validity that has been revealed for several tests of social cognition, and provides a framework for the assessment of social cognition.

Background Neuropsychiatric symptoms (NPS) are prevalent in the early clinical stages of Alzheimer’s disease (AD) according to proxy-based instruments. Little is known about which NPS clinicians report and whether their judgment aligns with proxy-based instruments. We used natural language processing (NLP) to classify NPS in electronic health records (EHRs) to estimate the reporting of NPS in symptomatic AD at the memory clinic according to clinicians. Next, we compared NPS as reported in EHRs and NPS reported by caregivers on the Neuropsychiatric Inventory (NPI). Methods Two academic memory clinic cohorts were used: the Amsterdam UMC ( n  = 3001) and the Erasmus MC ( n  = 646). Patients included in these cohorts had MCI, AD dementia, or mixed AD/VaD dementia. Ten trained clinicians annotated 13 types of NPS in a randomly selected training set of n  = 500 EHRs from the Amsterdam UMC cohort and in a test set of n  = 250 EHRs from the Erasmus MC cohort. For each NPS, a generalized linear classifier was trained and internally and externally validated. Prevalence estimates of NPS were adjusted for the imperfect sensitivity and specificity of each classifier. Intra-individual comparison of the NPS classified in EHRs and NPS reported on the NPI were conducted in a subsample (59%). Results Internal validation performance of the classifiers was excellent (AUC range: 0.81–0.91), but external validation performance decreased (AUC range: 0.51–0.93). NPS were prevalent in EHRs from the Amsterdam UMC, especially apathy (adjusted prevalence = 69.4%), anxiety (adjusted prevalence = 53.7%), aberrant motor behavior (adjusted prevalence = 47.5%), irritability (adjusted prevalence = 42.6%), and depression (adjusted prevalence = 38.5%). The ranking of NPS was similar for EHRs from the Erasmus MC, although not all classifiers obtained valid prevalence estimates due to low specificity. In both cohorts, there was minimal agreement between NPS classified in the EHRs and NPS reported on the NPI (all kappa coefficients < 0.28), with substantially more reports of NPS in EHRs than on NPI assessments. Conclusions NLP classifiers performed well in detecting a wide range of NPS in EHRs of patients with symptomatic AD visiting the memory clinic and showed that clinicians frequently reported NPS in these EHRs. Clinicians generally reported more NPS in EHRs than caregivers reported on the NPI.

Introduction:Behavioral and psychological symptoms in dementia (BPSD) have great impact on the daily lives of Alzheimer’s disease (AD) patients and their caregivers. Timely recognition and treatment of these symptoms may benefit quality of life, caregiver burden, and delay disease progression. In this qualitative study we examine the experiences of memory clinic physicians with the recognition and management of BPSD in early stages of AD.Methods:Semi-structured interviews were held with 8 physicians (5 neurologists, 3 geriatricians) employed at memory clinics of academic or general hospitals in the Netherlands. Two independent researchers coded verbatim transcripts of the interviews, followed by a consensus meeting on preliminary themes. In the upcoming months, additional interviews will be conducted until data saturation is reached.Results:Preliminary results indicate substantial variability in how memory clinic physicians recognize and diagnose BPSD in AD. Themes are: 1. Prevalence of BPSD in early stages of AD; e.g. ‘BPSD is more often present in late stages of AD […]’ vs. ‘I see this often, very often, I think these are the main problems people with AD face’). 2. Systematic assessment; some physicians consider it part of their clinical work-up to assess behavioral changes while other physicians do not touch upon BPSD. 3. Barriers for assessment; e.g. a lack of time, and not being able to observe BPSD occurring at home in a memory clinic setting. Treatment and management of BPSD in AD also differed greatly. Themes are 1. Treatment type; Two physicians discussed using a person-centered non-pharmacological approach, others refer patients with BPSD to daycare, a case manager or psychiatrist, or treat ‘problematic’ behaviors with psychotropic drugs. 2. Capabilities; some physicians experience managing BPSD in AD as very difficult, while others are confident about their capabilities. The majority suggests that collaboration with GPs or case managers may benefit treating these complex symptoms.Conclusion:There are remarkable differences in the recognition and management of BPSD in patients with AD visiting memory clinics in the Netherlands. Considering the potential benefit of early recognition and treatment, a first crucial step is discussing standardization of recognition and management of BPSD in memory clinics.

Purpose: The three variants of primary progressive aphasia (PPA) differ in clinical presentation, underlying brain pathology, and clinical course, which stresses the need for early differentiation. However, brief cognitive tests that validly distinguish between all PPA variants are lacking. The Sydney Language Battery (SYDBAT) is a promising screening instrument that can be used as a first step in a comprehensive neuropsychological assessment to distinguish PPA subtypes, but evidence on its validity and reliability is to date limited. In the current study, the validation and diagnostic value of the SYDBAT are described for discriminating PPA subtypes as well as distinguishing PPA from mild cognitive impairment (MCI) or Alzheimer's dementia (AD). Method: Forty-five patients with PPA (13 with semantic PPA, 20 with logopenic PPA, and 12 with nonfluent/agrammatic PPA), 25 MCI patients, 13 AD patients, and 50 cognitively unimpaired controls were included in this study. Both patients and controls completed the SYDBAT-NL (Dutch version). Performance on and predictive ability of the four subtests (i.e., Naming, Word Comprehension, Repetition, and Semantic Association) were assessed. In addition, construct validity and internal consistency were examined. Results: Different SYDBAT performance patterns were found across PPA and non-PPA patient groups. While a discriminant function analysis based on SYDBAT subtest scores could predict PPA subtype with 78% accuracy, it was more difficult to disentangle PPA from non-PPA patients based on SYDBAT scores alone. For assisting in clinical interpretation, simple rules were set up and translated into a diagnostic decision tree for subtyping PPA, which was capable of diagnosing a large proportion of the cases. Satisfying validity and reliability measures were found. Conclusions: The SYDBAT is an easy-to-use and promising screen for assessing single-word language processes, which may contribute to the differential diagnostic process of PPA and the assessment of language impairment in MCI and AD. It can be easily implemented for initial screening of patients in a memory clinic.

Background:Behavioral and psychological symptoms of dementia (BPSD) are very prevalent among individuals with dementia living in residential aged care. The development and implementation of new non-pharmacological interventions to reduce BPSD requires knowledge on the current perception and clinical practice of the care staff. We analyzed clinical care notes to examine the way residential aged care staff reported and managed BPSD in their daily clinical practice.Methods:We examined semi-structured care notes relating to the presentation and management of behaviors of 76 older residents (67% female; aged 67-101; 75% with formal dementia diagnosis) prior to participating in the Australian BPSDPLUS Program. As part of standard clinical practice in three residential aged care facilities, staff document the presentation and management of behaviors amongst residents. Using an inductive thematic analytical approach, we analyzed the reported data in the one and a half months prior to commencing participation in the BPSDPLUS Program. Care notes were coded and analyzed by two independent assessors and they discussed themes until consensus was reached.Results:A total of 465 behavior charts were completed in the one and a half months prior to the commencement of the BPSDPLUS Program. The number of behavioral charts varied widely across residents (Mean=7.3, range 0–93). Behaviors such as refusal of care, repetitive verbal behaviors, and wandering were most often mentioned, while apathy and affective and psychotic symptoms were seldomly reported. When confronted with BPSD, the clinical care notes indicated that care staff tend to respond in a reactive manner by reassuring, redirecting, or distracting the resident. Furthermore, it seems that staff did not routinely investigate potential underlying causes of the BPSD.Conclusions:These results suggest that the residential care staff primarily detected and responded to externalizing behaviors, while more internalizing behaviors were not reported. Potential underrecognition of internalizing behaviors, as well as the fact that the staff did not routinely examine causes of BPSD are vital observations for the development and implementation of nonpharmacological interventions and care programs targeting BPSD in residential aged care.

Background Neuropsychiatric symptoms (NPS) are very common in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia and are associated with various disadvantageous clinical outcomes including a negative impact on quality of life, caregiver burden, and accelerated disease progression. Despite growing evidence of the efficacy of (non)pharmacological interventions to reduce these symptoms, NPS remain underrecognized and undertreated in memory clinics. The BEhavioural symptoms in Alzheimer’s disease Towards early Identification and Treatment (BEAT-IT) study is developed to (1) investigate the neurobiological etiology of NPS in AD and (2) study the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) approach to structure and standardize the current care of NPS in AD. By means of the DICE method, we aim to improve the quality of life of AD patients with NPS and their caregivers who visit the memory clinic. This paper describes the protocol for the intervention study that incorporates the latter aim. Methods We aim to enroll a total of 150 community-dwelling patients with MCI or AD and their caregivers in two waves. First, we will recruit a control group who will receive care as usual. Next, the second wave of participants will undergo the DICE method. This approach consists of the following steps: (1) describe the context in which NPS occur, (2) investigate the possible causes, (3) create and implement a treatment plan, and (4) evaluate whether these interventions are effective. Primary outcomes are the quality of life of patients and their caregivers. Secondary outcomes include NPS change, caregiver burden, caregivers’ confidence managing NPS, psychotropic medication use, the experiences of patients and caregivers who underwent the DICE method, and the cost-effectiveness of the intervention. Conclusions This paper describes the protocol of an intervention study that is part of the BEAT-IT study and aims to improve current recognition and treatment of NPS in AD by structuring and standardizing the detection and treatment of NPS in AD using the DICE approach. Trial registration The trial was registered on the Netherlands Trial Registry ( NTR7459 ); registered 6 September 2018.

Hearing loss affects 1 in 5 people worldwide and is estimated to affect 1 in 4 by 2050. Treatment relies on the accurate diagnosis of hearing loss; however, this first step is out of reach for >80% of those affected. Increasingly automated approaches are being developed for self-administered digital hearing assessments without the direct involvement of professionals. This study aims to provide an overview of digital approaches in automated and machine learning assessments of hearing using pure-tone audiometry and to focus on the aspects related to accuracy, reliability, and time efficiency. This review is an extension of a 2013 systematic review. A search across the electronic databases of PubMed, IEEE, and Web of Science was conducted to identify relevant reports from the peer-reviewed literature. Key information about each report's scope and details was collected to assess the commonalities among the approaches. A total of 56 reports from 2012 to June 2021 were included. From this selection, 27 unique automated approaches were identified. Machine learning approaches require fewer trials than conventional threshold-seeking approaches, and personal digital devices make assessments more affordable and accessible. Validity can be enhanced using digital technologies for quality surveillance, including noise monitoring and detecting inconclusive results. In the past 10 years, an increasing number of automated approaches have reported similar accuracy, reliability, and time efficiency as manual hearing assessments. New developments, including machine learning approaches, offer features, versatility, and cost-effectiveness beyond manual audiometry. Used within identified limitations, automated assessments using digital devices can support task-shifting, self-care, telehealth, and clinical care pathways.

Because patients with stable coronary artery disease are at continued risk of major atherosclerotic events despite effective secondary prevention strategies, there is a need to continue to develop additional safe, effective and well-tolerated therapies for secondary prevention of cardiovascular disease. The LoDoCo (Low Dose Colchicine) pilot trial showed that the anti-inflammatory drug colchicine 0.5 mg once daily appears safe and effective for secondary prevention of cardiovascular disease. Colchicine's low cost and long-term safety suggest that if its efficacy can be confirmed in a rigorous trial, repurposing it for secondary prevention of cardiovascular disease would have the potential to impact the global burden of cardiovascular disease. LoDoCo2 is an investigator-initiated, international, multicentre, double-blind, event driven trial in which 5522 patients with stable coronary artery disease tolerant to colchicine during a 30-day run-in phase have been randomized to colchicine 0.5 mg daily or matching placebo on a background of optimal medical therapy. The study will have 90% power to detect a 30% reduction in the composite primary endpoint: cardiovascular death, myocardial infarction, ischemic stroke and ischemia-driven coronary revascularization. Adverse events potentially related to the use of colchicine will also be collected, including late gastrointestinal intolerance, neuropathy, myopathy, myositis, and neutropenia. The LoDoCo2 Trial will provide information on the efficacy and safety of low-dose colchicine for secondary prevention in patients with stable coronary artery disease.

Patients with chronic coronary disease were randomly assigned to receive 0.5 mg of colchicine once daily or matching placebo. The incidence of the composite end point of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was significantly lower with colchicine than with placebo.